Predatory Clinical Trials

by Kamalakar Duvvuru / September 15th, 2011

It is the poor one who saves: Middle-class rich boy that I was, I never would have thought that it would be the poor who would be my salvation. Owing to the upbringing I had received at my mother’s hands, as well as the attitude of the church I had been attending up until that time, I had always thought that it was we rich and well-to-do who would be the ones to rescue the poor. The latter depended on us, it seemed, and our generosity was their salvation. Without us they would have been destined to death. What blindness was ours and mine! The truth was just the contrary…It was the poor who would be my salvation, and not I theirs. It was they who would put me back on my feet.

— Francis of Assisi

The poverty of our century is unlike that of any other. It is not, as poverty was before, the result of natural scarcity, but of a set of priorities imposed upon the rest of the world by the rich. Consequently, the modern poor are not pitied…but written off as trash. The twentieth-century consumer economy has produced the first culture for which a beggar is a reminder of nothing.

— John Berger

The essence of the statement of Francis of Assisi is very apt to the issue of “clinical trials and poor”, although he made it in a different context. John Berger’s statement provides the reason for using poor and vulnerable as “guinea pigs” for clinical trials.

Using poor and vulnerable for clinical trials is nothing new. This has been going on for a long time.

The US covert clinical trials on the poor and vulnerable in Guatemala came to light in 2010 after Wellesley College professor Susan Reverby stumbled upon archived documents outlining the experiment led by the US doctor John Cutler during 1946-1948. The Guatemalan study, which was never published, was interested in whether penicillin could be used not only as a cure of venereal diseases but also as a prophylaxis (to prevent the disease from spreading). Nearly 5500 people were subjected to diagnostic testing and more than 1300, including Guatemalan soldiers, prisoners, commercial sex workers and mental patients, were exposed to syphilis by human contact or inoculations.

Initially the researchers infected female Guatemalan commercial sex workers with gonorrhea or syphilis, and then encouraged them to have unprotected sex with soldiers or prison inmates. Neither were subjects told what the purpose of the research was nor were they warned of its potentially fatal consequences. When the researchers couldn’t create enough infection through commercial sex workers, they started to do inoculations.

Some of the experiments were shocking. For example, seven women with epilepsy, who were in Home for the Insane, were injected with syphilis below the back of the skull. Another female syphilis patient was infected with gonorrhea in her eyes and elsewhere, in order to see the impact of an additional infection. Six months later she died.

Within the group that was subjected to clinical trials there were 83 deaths, according to Stephen Hauser, a member of US presidential commission. “It was not an accident that this happened in Guatemala,” commission president Amy Gutmann said, “Some of the people involved (in the research) said we could not do this in our own country.” The US researchers “systematically failed to act in accordance with minimal respect for human rights and morality in conduct of research,” Gutmann said, citing “substantial evidence” of an attempted cover up.

The Guatemalan president Alvaro Colom has called these experiments conducted by the US National Institutes of Health “crimes against humanity”. The Guatemala Study nauseated ethicists on multiple levels. Beyond infecting subjects with terrible disease, it was clear that people in the study did not understand what was being done to them or were not able to give their consent. Scientists showed no interest in the rights of the subjects of research. Nuremberg Code says doing this kind of research on people who cannot give informed consent is immoral and a crime against humanity.

Many US medical researchers, however, considered people like prisoners, mental patients and poor African Americans (i.e. poor people of different ethnicity) not fully human. So they felt that it was legitimate to experiment on these sections of people who did not have full rights in society. So, for American scientists the question of violation of human rights did not arise. In a federally funded study in 1942 male patients at a state insane asylum in Ypsilanti, Michigan, were injected experimental flu vaccine and then exposed them to flu several months later. Some of the men were not able to describe their symptoms, raising questions about how well they understood what was being done to them. According to a report, the test subjects were “senile and debilitated”.

In another federally funded study in the 1940s, Dr. W. Paul Havens, a World Health Organisation expert on viral diseases, exposed men to hepatitis in a series of experiments, including one using mental patients from mental institutions in Middletown and Norwich, Connecticut.

From 1963 to 1966, researchers intentionally gave hepatitis to mentally retarded children housed at the Willowbrook State School in Staten Island, New York, in an attempt to track the development of the viral infection and to test gamma globulin against it. According to a report, parents were told that the only way their child could be admitted to Willowbrook was through the hepatitis unit.

For a study in 1957, when the Asian flu epidemic was spreading, US government researchers sprayed the virus in the noses of 23 inmates at Patuxent prison in Jessup, Maryland, to compare their reactions to those of 32 virus exposed inmates who had been given a new vaccine.

Conducting medical experiments on prisoners increased with the huge growth in the US pharmaceutical and health care industries in the late 1940s and 1950s. By the 1960s, at least half the states allowed prisoners to be used as medical “guinea pigs”. In the congressional hearings in 1973, pharmaceutical industry officials acknowledged they were using prisoners for testing because they were cheaper than chimpanzees.

As the supply of prisoners and mental patients dried up, and regulations in the industrially developed countries have been made more stringent due to public outcry, medical researchers of these countries looked to countries where clinical trials could be done more cheaply with fewer or virtually nonexistent regulations, easy availability of more number of poor and vulnerable people, and favourable epidemiological conditions. The weakness of local health care structures generates a docile patient pool, making the process easier.

As recently as 1990, according to the inspector general of the Department of Health and Human Services, US, a mere 271 trials were being conducted in foreign countries of drugs intended for American use. By 2008 the number had risen to 6485 – an increase of more than 2000%. A database being compiled by the National Institutes of Health has identified 58788 such trials in 173 countries outside the US since 2000. In 2008 alone, according to the inspector general’s report, 80% of the applications submitted to the FDA for new drugs contained data from foreign clinical trials. Increasingly, the pharmaceutical companies are doing 100% of their testing in other countries. The inspector general found that the 20 largest US based companies now conducted “one-third of their clinical trials exclusively at foreign sites.”

One of the favoured destinations for clinical trials is India, due to its appealing advantages such as its widely spoken English, skilled workforce, established medical infrastructure, favourable regulatory environment, minimum ethical oversight, shorter patient recruitment time and cost effectiveness. India has a vast pool of patients, and among them many are “treatment naïve” meaning they have never taken any medication for their illness. This is very important for clinical trials, because it lowers the risk of unforeseen drug interactions and avoids the troublesome process of weaning patients off one medication and onto another.

Enticed by a $30 billion lucrative business of clinical trials Indian government is aggressively scrambling to catch Big Pharma’s eye. By making favourable policy changes for clinical trials by foreign companies, India, the hub of outsourced labour, is positioning itself in a newly lucrative role: “guinea pig” to the world.

In 2005 the Indian government took a more controversial step, amending a long-standing law that limited the kind of trials that foreign pharmaceutical companies could conduct. That law allowed companies to test drugs on Indian patients only after the drugs had been proven safe in trials conducted in the country of origin. In January 2005 the government threw out that constraint. It started improving staff and infrastructure, and making regulatory changes to speed up processing of applications. Public hospitals are being promoted as clinical trial sites. Mostly it is the poor, who cannot afford to go to private hospitals, who make use of the services of public hospitals. This makes them vulnerable to the enticement of drug trials, as the doctor-patient relationship in India is unique. They may be easily influenced by the doctor’s advice. Patients may not question their doctor’s judgment. They may also believe that refusal to follow the doctor’s advice to enter a trial would affect their access to medical care. So there is scope for a direct conflict of interest, especially if physicians are paid recruitment fees and all-expenses paid conferences abroad trips as a reward for recruiting their patients into trials. At the same time, by conducting the clinical trials, the under-resourced public hospitals gain some equipment and money.

Dr. Samiran Nundy, former editor of the Indian Journal of Medical Ethics, expressed doubt about the effect of the Indian government’s decision to relax the laws governing drug trials by foreign companies. He said the decision will increase the number of large scale drug trials conducted in India and put more patients at risk of exploitation. “Too many researchers fail to declare conflicts of interest, and it is only too easy to buy up poor illiterate patients, who are unable to give truly informed consent, and recruit them to trials which are of little or no benefit to them and which fail to safeguard their interests,” he said.

The growth of the clinical-trial industry in India needs to be seen within the social and economic context of the country. According to the United Nations, 40 percent of people in India are illiterate. Illiteracy puts many at risk not knowing whether the treatment their doctor is prescribing is a regular treatment or a part of a clinical trial. Moreover, doctors are respected to the point of being revered. So the likelihood of a poor person questioning their doctor about a specific treatment is low.

With the onset of neoliberalism the gap between rich and poor in India is widening. About 830 million people live on less than 20 rupees a day. Poverty forces some to enroll in clinical trials as a way to make a living. Faced with the fewest options, poor patients are most likely to try or be forcibly volunteered for risky new treatments due to lack of basic, affordable health care. Dr. Kalantri bemoans what he sees as skewed clinical trial demographics. “Ninety percent of patients being recruited in India are poor,” he says, “That’s the reality. Trials enroll very few patients who are rich, literate and capable of asking awkward questions.” As a result the poor and illiterate bear the consequences of the experiments of new drugs.

In a way the policies of the Indian government are also contributing to the fate of the poor, and facilitating clinical trials in public hospitals. For more than a decade, government policy has been to reduce public support for health care services, and these services are under-resourced. Health economists have pointed out that only 15% of the 1500 billion rupees spent in the health sector in India comes from the government. 4% comes from social insurance and 1% from private insurance companies. The remaining 80% is spent by individuals using private services and without insurance. Two-thirds of health care users bear 100% of their health care expenses. 70% of these health care users are poor.

In August 2008, it was reported that 49 babies below the age of 12 months have died at India’s best known medical institute, the All India Institute of Medical Sciences (AIIMS). The babies have died since January 2006, following the administration of new drugs and therapies under clinical trials. According to the information obtained under the Right to Information Act by Rahul Verma of an NGO called the Uday Foundation for Congenital Defects and Rare Blood Groups, 4142 babies were used for clinical trials conducted by the Department of Pediatrics since 1st January 2006, out of which 2728 babies were under one year of age. In an interview published in Delhi based newspaper MetroNow on 22 August 2008 Dr. Veena Kalra, former HOD-Pediatrics, AIIMS, stated that she did not rule out the possibility that the deaths of 49 babies in clinical trials and parents belonging to economically weaker sections could be true. She took voluntary retirement in 2008. That means the majority of these clinical trials happened when she was the HOD of the pediatric department.

Two of the trial drugs – olmesartan and valsartan, meant for reducing blood pressure – have never been tried on patients below the age of 18 years, according to Dr. Chandra Gulhati, editor of the Monthly Index of Medical Specialities.

In 2010 an investigation by a women’s health rights group, SAMA, exposed gross ethical violations of a study, where nearly 23,500 tribal girls between ages of 10-14 years in Andhra Pradesh and Gujarat were given the Human Papilloma Virus (HPV) vaccine that prevents cervical cancer. The clinical trials were carried out by an international NGO, the Program for Appropriate Technology and Health (PATH), in collaboration with the Indian Council of Medical Research (ICMR) and the governments of Andhra Pradesh and Gujarat. Most of the tribal girls, who were used as “guinea pigs”, were staying in government hostels for tribal students. In Andhra Pradesh nearly 2800 consent forms were signed by either a hostel warden or a headmaster. The fact that teachers played a “primary role” in explaining and “obtaining consent” meant that the consent was obtained under coercion. The investigation by SAMA revealed some disturbing facts. Given their background of poverty and under-nourishment, the tribal girls were given vaccine. Moreover, the information brochure provided to them was in English. So neither they nor the health worker administering the vaccine to them could read and understand. This raises the ethical question of obtaining “informed consent” from these tribal girls or their parents. Doing this kind of research on people who cannot give informed consent is immoral and a crime against humanity.

The most important question is, what criteria did the researchers apply to select tribal girls for the study? Is it their poverty, illiteracy (of their parents) and vulnerability that drove the researchers, with an active complicity of the Indian government and the health officials, to conduct risky clinical trials on these poor tribal people? Because their poverty desist them from taking any legal action against the multinational companies and their collaborators such as the central and state governments and ICMR, if the clinical trials consume their life. This is what happened to the loved ones of the seven girls who died after receiving the vaccine. Their parents, knowing full well that their children died only after receiving the vaccine, could only grieve for their children and for their helplessness to demand justice. (Watch the documentary produced by Zeina Awad, a reporter for Al Jazeera’s “Fault Lines” programme. Her report, “Outsourced: Clinical Trials Overseas,” aired on Al Jazeera English).

When the very government, which is supposed to look after the welfare of its citizens and protect the weak and vulnerable from the vultures like pharmaceutical companies, colludes with profit-driven multinational companies, one can imagine the plight of marginalised sections like tribals in India.

SAMA’s exposure of the ethical violations of the clinical trials, followed by the public outcry, forced the Indian central government to set up an inquiry committee in order to pacify the public, but not to do anything that would hurt the lucrative clinical trials business or antagonise multinational pharmaceutical companies. For the government, pharmaceutical companies and researchers, money is more important than the lives of poor people. They don’t mind profiting at the expense of the health and life of poor tribal girls. The committee did not indict either the drug company or the organisation that conducted the study. The inquiry concluded that the seven deaths were “most probably unrelated to the vaccine” and “the cause of death in all the cases cannot be established with certainty.” It observed “several minor deficiencies in the planning and conduct of the study”. But the reality is these “minor deficiencies” caused the death of seven innocent tribal students. The “minor deficiencies” include no proper monitoring of the health of these girls for adverse effects of the drug.

According to Menaka Gandhi, a member of the Indian parliament, there is a growing number of clinical trial deaths – 137 deaths in 2007, 288 in 2008 and 637 in 2009. Imagine the uproar if so many clinical trial deaths happened in America or Europe. This can happen only elsewhere as a result of the drug trials conducted by the American and European pharmaceutical companies.

According to an investigation, pharmaceutical companies conducting clinical trials in India have not compensated for the clinical trial deaths. Of 671 deaths that were reported in 2010, there is evidence that compensation was paid in just three cases. The Indian health ministry has asked 44 pharmaceutical companies, including Eli Lilly, Novartis, Pfizer, Bayer, Merck, Johnson & Johnson and Sanofi-Aventis, to explain why they have not paid compensation. For example, data compiled by the ministry show there were 152 deaths reported during Sanofi trials and 138 in Bayer trials. What is interesting is the answer given by the companies or the researchers whenever clinical trial deaths happened. A Novartis spokesperson told that its clinical trial investigation found that deaths were not caused by the trial drug, but instead due to the progression of underlying diseases. So compensation was not paid in such cases. Other pharmaceutical companies also offered similar argument. For the deaths of 49 babies, AIIMS presented similar defense, saying that no death was “attributable to the study treatments used” and “the deaths were due to the natural history of the severe disease that the children suffered from.” This is the conclusion also of the inquiry committee set up by the Indian central government on the deaths of the vaccine for cervical cancer: “(The seven deaths were) most probably unrelated to the vaccine…(and) the cause of death in all the cases cannot be established with certainty.”

In this light, outsourcing drug trials to a country where decent medical care is scarce and cost of medicine is beyond the reach of the poor, is just the globalization and continuation of the same old equation – poor and vulnerable of different ethnicity are not fully human, and so can be used as “guinea pigs” for clinical trials to extend life of the rich, and to produce more profits for the pharmaceutical companies and the facilitators like government policy-makers and medical professionals at the expense of the health and life of the poor (the same attitude may be seen even in the past and present American and European imperial wars). India is able to provide significant cost savings of 50-60% for clinical trials. No wonder the clinical trials market in India has been expanding at an astounding 36% annually from 2006-07 to 2010-11, according to a study conducted by the Centre for Studies in Ethics and Rights, Mumbai. The study, however, shows that the increase in clinical trials has no correlation to the disease scenario in the country. Most trials are of relatively expensive drugs offering only marginal benefit over existing ones. 13.4% of drug trials is for cancer drugs, although cancer is not among the top ten killers in India. But it is among the top ten in industrially developed countries. According to the study, trials on perinatal conditions, a major cause for deaths in India, constitute just 2.9%. Only 16 out of 1078 drug trials were on lower respiratory tract infections, although they are among the biggest killers both in India and other developing countries, the study observes.

What the majority of Indians need is basic, affordable health care and nutrition. In India Article 21 of Fundamental Rights assures the right to live with dignity. The state is under a constitutional obligation to see that there is no violation of the fundamental right of any person, particularly when she/he belongs to weaker sections of the society, either by failing to provide the basic health care and nutrition, or by facilitating (or colluding with) vultures like pharmaceutical companies to exploit marginalised people in the society.